The action of 5 alpha-dihydrotestosterone and antiandrogens on the activities of 5 alpha-reductase and 3 alpha-hydroxysteroid dehydrogenase in the pituitary gland of gonadectomized rats.
In gonadectomized rats of either sex s.c. administration of 5 alpha-dihydrotestosterone (DHT) reversed, in a dose dependent manner, effects brought about by gonadectomy: it decreased pituitary wet weight and serum levels of LH and FSH and suppressed microsomal enzyme activities involved in testosterone and progesterone metabolism in the pituitary gland, NADPH-linked 5 alpha-reductase and NADH-linked 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSDH). Concomitantly administered nonsteroidal antiandrogen, flutamide (5 mg/day), antagonized some of the suppressive effects induced by a 14-day treatment of gonadectomized rats with high dose (1 mg/day) of DHT. It completely blocked DHT action on pituitary 5 alpha-reductase activity in the female rat and, in the male, inhibition was found to be 30-35%. In male, but not female rats, it completely blocked DHT suppression of serum FSH level whereas it slightly, but significantly inhibited DHT suppression of serum LH in rats of either sex. However, flutamide did not prevent DHT suppression of pituitary wet weight or NADH-linked 3 alpha-HSDH activity. Concomitantly administered progestational antiandrogen, cyproterone acetate (5 mg/day), inhibited DHT-induced weight increase of seminal vesicles by 50-55% and completely blocked the weight decrease of pituitary gland but did not antagonize DHT suppression of serum gonadotropins or pituitary enzyme activities. The results obtained with flutamide suggest that DHT-induced suppression of pituitary NADPH-linked 5 alpha-reductase, but not NADH-linked 3 alpha-HSDH activity, might involve an androgen receptor mechanism.
D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism*; D000726:Androgen Antagonists / Q000494:pharmacology*; D000818:Animals; D002369:Castration; D013196:Dihydrotestosterone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010088:Oxidoreductases / Q000378:metabolism*; D010902:Pituitary Gland / Q000201:enzymology*; D051381:Rats
D000726:Androgen Antagonists; D013196:Dihydrotestosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D010088:Oxidoreductases; D015096:3-Hydroxysteroid Dehydrogenases; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase